Catheter-associated urinary tract infections (CAUTIs) are one of the most common nosocomial infections and if untreated can lead to serious complications including bacteremia and death. Enterococcus faecalis is one of the leading causative agents of CAUTI and its treatment has become increasingly difficult due to its ability to disseminate in hospital settings, adhere and form biofilms on catheters and other indwelling medical devices, and its inherent and acquired resistance to multiple antibiotics. The poor understanding of the molecular details of CAUTI pathogenesis has limited the development of new therapies to prevent and treat this infection. In a mouse model of CAUTI, which replicates many aspects of human clinical CAUTI, we have shown that urinary catheterization elicits bladder inflammation, edema, production of inflammatory cytokines, and neutrophil recruitment, while paradoxically, providing a bladder environment in which E. faecalis can thrive. I have found that host fibrinogen (Fg), which is released upon catheter-induced inflammation, is critical for E. faecalis adherence to catheters and for promoting growth and biofilm formation on catheters within the bladder. These findings suggest that manipulating the host inflammatory environment to limit inflammation and/or Fg release into the bladder lumen upon catheterization may be an effective strategy to greatly reduce the incidence of CAUTI. Further, while Fg seems to promote E. faecalis infection in CAUTI, in other systems it has been shown that Fg is a proinflammatory molecule that is induced by IL-1, IL-6, and TNF? it is linked to multiple human inflammatory diseases. This raises additional questions of how E. faecalis is able to exploit the inflamed bladder environment and withstand host defense mechanisms to colonize the catheterized bladder. Furthermore, neutrophils are the most abundant immune cells during CAUTI and despite their presence E. faecalis is able to persist in the bladder. It is unclear why neutrophils are unable to completely clear the infection. Several reports have shown that Fg binds to neutrophils suppressing the apoptosis pathway, which is important for bacterial phagocytosis and clearance, and for resolution of the inflammation. Therefore I hypothesize that during CAUTI E. faecalis exploits the release of fibrinogen due to the inflammatory response to catheterization for persistence and for circumvention of neutrophil bactericidal function and that limiting inflammation will decrease E. faecalis CAUTI. My first Aim will investigate the contribution of inflammatory cytokines to the release and accumulation of Fg in the bladder and their role in E. faecalis persistence. My second Aim will examine the role of Fg in modulating neutrophil activity and the contribution of this interaction to E. faecalis immune evasion during CAUTI. Elucidation of E. faecalis-host interaction mechanisms is needed to understand CAUTI pathophysiology in order to uncover possible strategies to efficiently prevent host inflammation and treat E. faecalis infection. These results will be of significant importance for patients that require acute or prolonged catheterization.